Association of tryptophan metabolites with incident type 2 diabetes in the PREDIMED trial: A case–cohort study

Identifier:  imarina:3992546

Handle: https://hdl.handle.net/20.500.11797/imarina3992546

Authors:  Yu, Edward; Papandreou, Christopher; Ruiz-Canela, Miguel; Guasch-Ferre, Marta; Clish, Clary B; Dennis, Courtney; Liang, Liming; Corella, Dolores; Fito, Montserrat; Razquin, Cristina; Lapetra, Jose; Estruch, Ramon; Ros, Emilio; Cofan, Montserrat; Aros, Fernando; Toledo, Estefania; Serra-Majem, Lluis; Sorli, Jose V; Hu, Frank B; Martinez-Gonzalez, Miguel A; Salas-Salvado, Jordi

Abstract:
© 2018 American Association for Clinical Chemistry. BACKGROUND: Metabolites of the tryptophan– kynurenine pathway (i.e., tryptophan, kynurenine, kynurenic acid, quinolinic acid, 3-hydroxyanthranilic) may be associated with diabetes development. Using a case– cohort design nested in the Prevención con Dieta Mediterránea (PREDIMED) study, we studied the associations of baseline and 1-year changes of these metabolites with incident type 2 diabetes (T2D). METHODS: Plasma metabolite concentrations were quantified via LC-MS for n 641 in a randomly selected subcohort and 251 incident cases diagnosed during 3.8 years of median follow-up. Weighted Cox models adjusted for age, sex, body mass index, and other T2D risk factors were used. RESULTS: Baseline tryptophan was associated with higher risk of incident T2D (hazard ratio 1.29; 95% CI, 1.04 –1.61 per SD). Positive changes in quinolinic acid from baseline to 1 year were associated with a higher risk of T2D (hazard ratio 1.39; 95% CI, 1.09 –1.77 per SD). Baseline tryptophan and kynurenic acid were directly associated with changes in homeostatic model assessment for insulin resistance (HOMA-IR) from baseline to 1 year. Concurrent changes in kynurenine, quinolinic acid, 3-hydroxyanthranilic acid, and kynurenine/tryptophan ratio were associated with baseline-to-1-year changes in HOMA-IR. CONCLUSIONS: Baseline tryptophan and 1-year increases in quinolinic acid were positively associated with incident T2D. Baseline and 1-year changes in tryptophan metabolites predicted changes in HOMA-IR. Tryptophan levels may initially increase and then deplete as diabetes progresses in severity.